GHK-Cu

Glycyl-L-histidyl-L-lysine complexed with Cu(II), an endogenous tripeptide present in plasma, saliva, and urine, first isolated from human plasma albumin by Loren Pickart in 1973. Plasma concentration declines from roughly 200 ng/mL at age 20 to around 80 ng/mL at 60, paralleling reduced dermal elasticity, slower wound repair, and follicular miniaturisation.

Topical GHK-Cu (INCI: Copper Tripeptide-1) is an unrestricted cosmetic ingredient. The injectable is a research chemical, not FDA-approved, and was placed on the FDA Category 2 bulk drug substances list in 2023, restricting 503A compounding on the basis of insufficient human safety data for parenteral routes.

This page covers the oral presentation. Available information is minimal. Oral guidance consists of a cycle specification (8–12 weeks, 4-week washout), a timing note, a fasting preference, and a single dosing line. No dose form, no per-unit strength, no oral bioavailability figure, and no bioequivalence claim in either direction.

The pharmacological question an oral route raises — whether a copper-chelated tripeptide survives gastric acid and brush-border peptidases intact, and whether Cu(II) remains bound through absorption and first-pass hepatic handling — is not addressed by any cited study. Human data are almost entirely topical; systemic data are almost entirely animal and injectable. All mechanistic and outcome content below is attributed to those routes, not established for this one.

Mechanisms below are established in vitro, in animal models, and by inference from topical and injectable use; none has been demonstrated for enteral administration.

Copper cofactor delivery. Cu(II) is required by lysyl oxidase for collagen and elastin cross-linking, and by enzymes of antioxidant defence and energy production. GHK-Cu presents bioavailable copper to tissue without the toxicity of free ionic copper.

Gene expression modulation. Broad Institute Connectivity Map analysis across more than 7,000 profiles found GHK induces a 50% or greater expression change in 31.2% of human genes, upregulating repair, antioxidant, and DNA repair genes (47 and 14 respectively) and downregulating inflammatory and catabolic programmes. In a metastatic colon cancer signature, GHK reversed 70% of overexpressed genes among 1,309 molecules screened. Activity is observed at picomolar to nanomolar concentrations.

ECM synthesis. Fibroblast upregulation of type I and III collagen, elastin, glycosaminoglycans, and decorin, the latter organising collagen fibril architecture.

MMP/TIMP regulation. In culture, GHK-Cu increased MMP1 and MMP2 alongside TIMP1 at all tested concentrations; the shifted TIMP-to-MMP ratio correlated with increased collagen and elastin output.

Anti-inflammatory and antioxidant. Reduced TNF-alpha, IL-6, and IL-1 beta; activation of endogenous antioxidant systems; restored viability of irradiated fibroblasts. Pickart et al. (2015) describe activation of TGF-beta and integrin pathways in regeneration.

Angiogenesis. VEGF release, mechanistically adjacent to BPC-157's VEGFR2 effects.

Chemotaxis and stem cell activation. Recruitment of macrophages, mast cells, and fibroblasts; reported 160% increase in stem cell growth.

Serum half-life is under one hour, favouring frequent low doses over sporadic large ones. Oral proteolytic stability and copper retention through absorption are unaddressed.

The oral presentation makes no claims of its own. The following is the compound's documented activity via topical and parenteral routes.

Elastin and collagen synthesis; improved dermal hydration; restored elasticity with reversal of age-related dermal thinning; reduction of wrinkles, photodamage, and hyperpigmentation; reduced oxidative damage and UV photoprotection (70% keratinocyte viability versus 40% in controls after UV); anti-inflammatory and antioxidant activity.

Accelerated wound closure with improved contraction, granulation, epithelialisation, collagen deposition, and reduced scarring; systemic injection improves healing at distant sites. Repair support across dermal, pulmonary connective, osseous, hepatic, gastrointestinal mucosal, tendon, ligament, and neural tissue. Follicular enlargement and dermal papilla proliferation; hair thickness outcomes are inconsistent in practice. Restoration of tight junction proteins (ZO-1, Occludin) and mucosal healing via SIRT1/STAT3 in a murine colitis model.

Transferability caveat. These outcomes are anchored to topical concentrations of 0.5% to 4% and to a 1–2 mg/day subcutaneous practice dose. No oral strength, bioavailability, or dose equivalence is given. The fasted-dosing preference — 30–60 minutes before food or drink — is the only implicit acknowledgement that oral absorption is a constraint.

No oral-route timelines exist. The following are topical trial timepoints and user reports from injectable use.

Published timepoints. Topical application for 8 weeks: 55.8% reduction in wrinkle volume, 32.8% in depth. Twelve weeks: measurable gains in density, thickness, and firmness with reduced fine lines and sagging. Topical hair effects require 16 to 24 weeks. In the rat ACL model, improvement at 6 weeks did not persist at 12 weeks after discontinuation.

Serum half-life is under one hour; frequent low doses maintain more stable tissue exposure than sporadic large ones.

Users report (injectable). Weeks 1–2: improved texture, softness, early glow. Weeks 4–6: reduced fine lines, increased skin thickness, improved complexion; some report minor injury healing or reduced joint discomfort. One report describes crepey skin resolving after a 6-week run at 2 mg daily. Weeks 8–12: reduced wrinkle depth, improved firmness, fading lentigines; one long-term user described dry photodamaged skin becoming soft by 6 weeks with continued gains to 3 months on a blend.

Hair outcomes are inconsistent: faster growth without thickness change is common, and injectable use alone frequently yields nothing; microneedling combinations produce more consistent results in practice. Healing reports are heavily confounded by co-administration with BPC-157 and TB-500.

Non-response occurs: one user saw no skin or hair change across 2 months at 3 mg daily followed by 2 months at 5 mg daily.

For the oral route, exposure is unquantified, so these timelines should be treated as an upper bound rather than an expectation.

Oral specification, complete. One unit per day, daily, for 8–12 weeks; 4-week washout; any time of day or night; fasted preferred (at least 30–60 minutes before food or drink) but not mandatory. Dose form, per-unit strength, titration, ceiling, oral bioavailability, and equivalence to the injectable are all absent. Strength is available only from the product label.

Reference points from other routes. Standard subcutaneous practice: 1 to 2 mg per day, daily or 5 days per week, 4 to 8 weeks (extendable to 12), 4 to 6 weeks between cycles. Conservative entry: 0.5 to 1 mg per day, 3 to 5 times per week, to assess tolerance. Reconstitution of a 50 mg vial in 2.5 to 3 mL bacteriostatic water; at 2.5 mL, 1 mg = 5 units on an insulin syringe; blue colouration from copper is expected. Topical: 0.5% to 4% facial, 2% periorbital, once or twice daily, continuous without cycling, 8 to 16 weeks for skin and 16 to 24 weeks for hair. Animal injectable work used approximately 0.5 to 1.5 mg/kg. No published dose-finding exists for subcutaneous practice, and nothing at all for oral.

The oral cycle's 4-week washout is shorter than the injectable's 4–6 weeks; whether this reflects lower systemic exposure or merely a different convention cannot be determined.

Serum half-life under one hour favours consistent daily administration over sporadic larger doses. Introduce GHK-Cu as the sole new compound to attribute any adverse response. No oral protocol is given below because none has been described for this route.

No published study addresses oral GHK-Cu. Human evidence is confined to topical application; systemic evidence is preclinical.

Topical, human. Badenhorst et al. (2016), randomised double-blind, N=40 women aged 40 to 65, twice-daily GHK-Cu in lipid-based nanocarriers for 8 weeks: 55.8% reduction in wrinkle volume (p<0.001), 32.8% reduction in wrinkle depth (p=0.012) versus control serum, and 31.6% wrinkle volume reduction versus Matrixyl 3000 (p=0.004); in vitro arm showed increased collagen and elastin with a favourable TIMP-to-MMP shift. Finkley et al. (2005), 12 weeks, N=71 women with mild to advanced photoaging, twice-daily cream: improved density and thickness, reduced fine lines and sagging, no adverse events; published as a book chapter. Abdulghani et al. (1998): collagen production improved in 70% of women versus 50% with vitamin C and 40% with retinoic acid. Kang et al. (2009), in vitro: increased integrin alpha-6 and beta-1 and p63 positivity in keratinocytes. Pyo et al. (2007), in vitro hair follicle elongation, used AHK-Cu rather than GHK-Cu.

Systemic, animal. Maquart et al. (1993), rat wound chambers: concentration-dependent collagen synthesis roughly twice that of noncollagen proteins, with increased Type I and III collagen mRNA. Fu et al. (2015), N=48 rats, intra-articular GHK-Cu after ACL reconstruction: reduced knee laxity at 6 weeks, not sustained at 12 weeks after discontinuation. Mao et al. (2025), N=32 BALB/c mice, DSS colitis: restored ZO-1 and Occludin, suppressed TNF-alpha, IL-6 and IL-1 beta, mucosal healing via SIRT1/STAT3. Dou et al. (2020): improved learning in aged mice.

Mechanistic reviews. Pickart and Margolina (2018): Connectivity Map data showing GHK induces a 50% or greater expression change in 31.2% of human genes, reversal of 70% of overexpressed genes in a metastatic colon cancer signature, and upregulation of 47 DNA repair and 14 antioxidant genes at picomolar to nanomolar concentrations. Pickart et al. (2015): TGF-beta and integrin pathway activation, reduced TNF-alpha-induced IL-6. Pickart et al. (2012): review on oxidative stress and cognitive ageing.

Gaps. No dose-finding studies for subcutaneous use; no human safety or efficacy data for injectable use; nothing whatsoever on enteral bioavailability, gastric stability of the copper complex, or dose equivalence. Serum half-life is under one hour, which is the rationale for frequent lower doses.